Arginine infusion is known to increase the plasma levels of both imniunoreactive insulin and glucagon, while it changes the plasma glucose concentration only slightly. In order to clarify the metabolic consequences of glucagon and insulin mobilization induced by arginine, we investigated the effects of this amino acid on the turnover and plasma concentration of glucose, and on the plasma concentration of free fatty acids (FFA) in seven normal dogs. Infusion of arginine hydrochloride induced a biphasic release of insulin, which in turn increased the over-all rate of glucose utilization by 40 per cent. There was, however, only a slight increase in plasma glucose concentration (4 per cent) since the rate of glucose production increased to the same extent as the rate of glucose utilization. We have concluded that the biphasic pattern of insulin release not only reflects the secretory capacity of β cells, but also plays an essential metabolic role in maintaining a balance between the production and utilization of glucose during an arginine challenge. The observed increase in glucose production is attributed to the release of glucagon; this release is essential if normoglycemia is to be maintained. The concentration of FFA in plasma decreased by 50 per cent during infusion of the amino acid. In the dog, arginine infusion rapidly reverses the pattern of fuel utilization characteristic of fasting; the release of free fatty acids from fat depots is inhibited, while the turnover of glucose is enhanced even though normoglycemia is maintained.